Molecular evidence that oral supplementation with lycopene or lutein protects human skin against ultraviolet radiation: results from a double-blinded, placebo-controlled, crossover study.

BACKGROUND: Increasing evidence suggests photoprotection by oral supplementation with ß-carotene and lycopene. OBJECTIVES: To examine the capacity of lycopene-rich tomato nutrient complex (TNC) and lutein, to protect against ultraviolet (UV)A/B and UVA1 radiation at a molecular level. METHODS: In a placebo-controlled, double-blinded, randomized, crossover study two active treatments containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 the radiation-inducible genes HO1, ICAM1 and MMP1. Sixty-five healthy volunteers were allocated to four treatment groups and subjected to a 2-week washout phase, followed by two 12-week treatment phases separated by another 2 weeks of washout. Volunteers started either with active treatment and were then switched to placebo, or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 h later biopsies were taken from untreated, UVA/B- and UVA1-irradiated skin for subsequent reverse transcriptase polymerase chain reaction analysis of gene expression. Moreover, blood samples were taken after the washout and the treatment phases for assessment of carotenoids. RESULTS: TNC completely inhibited UVA1- and UVA/B-induced upregulation of heme-oxygenase 1, intercellular adhesion molecule 1 and matrix metallopeptidase 1 mRNA, no matter the sequence (anova, P < 0·05). In contrast, lutein provided complete protection if it was taken in the first period but showed significantly smaller effects in the second sequence compared with TNC. CONCLUSIONS: Assuming the role of these genes as indicators of oxidative stress, photodermatoses and photoageing, these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women.

INTRODUCTION AND OBJECTIVES: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. MATERIALS AND METHODS: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. RESULTS: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. CONCLUSIONS: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

[Topical application of vitamins, phytosterols and ceramides. Protection against increased expression of interstital collagenase and reduced collagen-I expression after single exposure to UVA irradiation]. / Topische Applikation von Vitaminen, Phytosterolen und Ceramiden. Schutz vor vermehrter Expression der interstitiellen Kollagenase und verminderter Kollagen-I-Expression nach 1-maliger UVA-Bestrahlung.

Photoaged skin is characterized by a decrease of dermal collagen fibers, resulting from an increased breakdown and a diminished de novo synthesis. The increased breakdown results from an increased expression of matrix metalloproteinases (MMPs). The main building blocks involved in de novo synthesis of collagen fibers are collagen 1A1 and 1A2, the expression of which is reduced in photoaged skin. We studied the effect of topical application of vitamins, phytosterols and ceramides on UV-induced up-regulation of the expression of MMP-1 and on UV-induced down-regulation of COL1A1 and COL1A2. The study was conducted with 10 subjects with healthy skin who were comparatively treated for 10 days with (i) a basic preparation containing jojoba oil, (ii) the basic preparation supplemented with vitamins, (iii) the basic preparation supplemented with phytosterols and ceramides, and (iv) the basic preparation supplemented with vitamins, phytosterols and ceramides. All four preparations inhibited the UV induced up-regulation of MMP-1. Neither the basic product nor that supplemented with vitamins inhibited down-regulation of COL1A1 and COL1A2, but addition of phytosterols and ceramides caused a decreased down-regulation of the expression of these genes. Our results indicate that phytosterols and ceramides are effective in blocking the reduced collagen synthesis after UV irradiation and even stimulating synthesis. They may be useful additions to anti-aging products.

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin.

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.